Immune selection of equine infectious anemia virus env variants during the long-term inapparent stage of disease
| Autor: | Susan Carpenter, Amanda K. Antons, Yvonne Wannemuehler, Brett A. Sponseller, Wendy O. Sparks, Yuxing Li, J. Lindsay Oaks |
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| Rok vydání: | 2007 |
| Předmět: |
Time Factors
Genotype Lentivirus persistence Molecular Sequence Data Clone (cell biology) Virulence Biology Virus Cell Line Evolution Molecular Equine infectious anemia 03 medical and health sciences Dogs Immune system Neutralization Tests Virology Equine infections anemia virus Antigenic variation Animals Amino Acid Sequence Horses Selection Genetic Neutralizing antibody 030304 developmental biology 0303 health sciences 030306 microbiology Gene Products env Genetic Variation biology.organism_classification 3. Good health Equine Infectious Anemia Broadly neutralizing antibody Acute Disease Carrier State Chronic Disease Disease Progression biology.protein Infectious Anemia Virus Equine |
| Zdroj: | Virology. 363(1):156-165 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2007.01.037 |
| Popis: | The principal neutralizing domain (PND) of equine infectious anemia virus (EIAV) is located in the V3 region of SU. Genetic variation in the PND is considered to play an important role in immune escape and EIAV persistence; however, few studies have characterized genetic variation in SU during the inapparent stage of disease. To better understand the mechanisms of virus persistence, we undertook a longitudinal study of SU variation in a pony experimentally inoculated with the virulent EIAVWyo. Viral RNA isolated from the inoculum and from sequential sera samples was amplified by RT-PCR, cloned, and individual clones were sequenced. Of the 147 SU clones obtained, we identified 71 distinct V3 variants that partitioned into five major non-overlapping groups, designated PND-1 to PND-5, which segregated with specific stages of clinical disease. Genotypes representative of each group were inserted into an infectious molecular clone, and chimeric viruses were tested for susceptibility to neutralization by autologous sera from successive times post-infection. Overall, there was a trend for increasing resistance to neutralizing antibody during disease progression. The PND genotype associated with recrudescence late in infection was resistant to both type-specific and broadly neutralizing antibody, and displayed a reduced replication phenotype in vitro. These findings indicate that neutralizing antibody exerts selective pressure throughout infection and suggest that viral strategies of immune evasion and persistence change in the face of an evolving and maturing host immune response. |
| Databáze: | OpenAIRE |
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